1. Technical Field
The present invention relates to the field of bone cements and specifically concerns a radiopaque acrylic bone cement having improved mechanical characteristics and a method for its preparation.
The bone cement according to the invention is therefore suitable for use advantageously in surgery where the combination of a high degree of radiopacity and notable mechanical strength are required.
More particularly, the present invention relates to a bone cement which is suitable in particular for applications in vertebroplasty, cranioplasty, maxillofacial surgery and for fixing prostheses in orthopaedic surgery.
2. Background Art
In the orthopaedic surgery sector, bone cements composed of a mixture of resins biocompatible with the bone tissues are known and commonly used for stably fixing prostheses of different types in a wide range of locations on the skeleton or for restoring the continuity of tissues.
The most commonly used resins belong to the acrylic materials. The more widely used bone cements are composed of two phases, a liquid phase substantially composed of methyl methacrylate with an addition of N,N-dimethyl-p-toluidine as accelerator and hydroquinone as stabilizer, and a solid phase composed of a dry powder substantially composed of poly(methyl methacrylate) with a peroxide, usually benzoyl peroxide, as polymerization initiator. At the moment of use, the two phases are mixed, the polymer powder representing the solid phase is dissolved in the monomer present in the liquid phase, giving a liquid viscous solution. In the meantime, the N,N-dimethyl-p-toluidine causes the peroxide to decompose with the formation of free radicals which initiate the polymerization reaction, resulting in hardening of the mixture.
In addition to poly(methyl methacrylate), bone cements are known which contain a solid phase containing resins of the poly(ethyl methacrylate), poly(butyl methacrylate), poly(methyl methacrylate/styrene) types and/or copolymers thereof, which belong to the class of acrylic resins.
The effect of the bone cement consists in completely filling the voids present between the prostheses and the bone cavity prepared for implantation thereof, so as to ensure mechanical anchoring and a perfect fit of the bone implant.
The mechanical strength of the hardened cement thus obtained is not as high as that of the original bone tissues. Indeed, as a result of the considerable loads or as a result of fatigue stress at a high cycle number, the bone cement fillings can give way and fracture. The modification of such fillings with time, their eventual flaking-off and their mechanical weakening must therefore be able to be detected and monitored, for example using standard radiological and tomographic techniques.
Since the synthetic base resin is transparent to X-rays, the bone cement must be rendered opaque by adding suitable inorganic biocompatible substances.
The opacity to X-rays of the elements increases substantially in proportion to their atomic weight. In general, especially for the heavier elements, their toxicity also increases. In medicine the known and most commonly used contrast agents are iodine, either in elemental or bonded form, bismuth in the form of carbonate and barium in the form of sulphate.
By using compounds such as salts or oxides, the radiopaque element constitutes only a portion of the additive. For example, the metal amounts to only 58% of barium sulphate, the remaining material being substantially transparent to X-rays.
In the known bone cements, such radiopacifying materials usually consist of barium sulphate or zirconium oxide additives, in an amount of about 10% by weight, relative to the dry polymer.
Such additives, which introduce discontinuities in the polymer, weaken further the mechanical properties of the hardened cement, increasing the risk of failure and frequency of fracturing or flaking off.
With the aim of reducing such disadvantages, the teachings of U.S. Pat. No. 5,795,922 propose encapsulation of the radiopacifying substance, in this case selected from the group consisting of barium salts, zirconium oxide and bismuth glasses, in microcapsules of a compatible polymer material. During formation of the bone cement, the polymer material dissolves completely in the liquid phase releasing its contents, the radiopaque substance, which is enveloped by the polymer being formed.
These known bone cements are not suitable for the treatment of certain disorders, for example, in the case of vertebroplasty.
Indeed, in the case of disorders of the general tumour type, in which an emptying of the vertebra structure is produced, the latter loses its mechanical strength and collapses under the body weight, resulting in crushing of the nerve endings, causing intense suffering of the patient and a partial loss of motor function.
At the present time, in accordance with the prior art hitherto, such disorders are treated with prostheses, metal plates or by administering analgesics.
A further known technique for such disorders consists in opening the vertebra, introducing the bone cement of the type described above, and closing it again. The hardened bone cement substitutes the missing part of the vertebra.
Recently, a new technique has been proposed which consists in injecting liquid bone cement, by means of a needle, inside the vertebra, thus avoiding the invasive surgical intervention referred to above.
This technique requires the use of a low-viscosity liquid bone cement so as to be able to inject it easily by means of a needle which may have a diameter of even less than 2 mm.
This operation is complicated and not free of risks since an error in positioning of the cement could result in a contact of the resin with the nerve endings of the spinal column, resulting in a paralysis of the patient or in a substantial increase in pain, owing to the insertion of protrusions in direct contact with the nerve centers which pass through the spinal column.
In order to be able to perform this operation with absolute safety, the surgeon must be well-informed of the state of progress of the injection, which is controlled in real time by means of X-rays. Since the time during which monitoring must take place is quite long, usually several hours, the intensity of exposure to the radiation must be extremely low. Accordingly, it is not possible to use radiological or tomographic techniques involving significant radiation doses, but instead fluoroscopic techniques in which the patient is subjected to low-intensity X-rays must be used.
The known bone cements described above, which are particularly suitable for the fixing of prostheses, have proved to be insufficiently opaque to low-intensity X-rays, poorly visible, practically transparent and substantially unsuitable for performing the injection with adequate safety.
The medico-scientific literature has reported several cases in which the surgeon has added an appreciable quantity of the radiopacifying contrast agent barium sulphate of up to 30–40% by weight, so as to render the cement used sufficiently radiopaque.
On the other hand, the use of a metal in the form of salt has the consequence that only 58% by weight of the material introduced has an actual radiopacifying effect.
The presence of a voluminous quantity of powdery radiopacifier in the acrylic matrix increases the probability of initiating fractures and thus undermines the integrity of the structure and jeopardizes the mechanical strength of the material in the long run (fatigue strength). This phenomenon is confirmed even in those cases in which the static performances comply with the minimum requirements of the ISO standard 5833.
In any case, this benefits the patient, but the intervention cannot guarantee that the expected result will be maintained over a long period, since the reinforcing structure is extremely weak.
The medico-scientific literature has described other cases in which the surgeon adds to the bone cement of the type described above containing approximately 10% by weight of barium sulphate, relative to the dry polymer, or approximately 15% by weight of zirconium oxide, relative to the dry polymer, a quantity of powdery tungsten amounting to about 2% by weight as further radiopacifier.
The addition of about 9% by weight of tantalum powder to a bone cement devoid of radiopacifiers is likewise known.
In all abovementioned cases, the addition is made directly by the surgeon, shortly before the intervention, under his responsibility and using a non-certified material. This has made it possible to improve the radiopacifying effect without decreasing excessively the mechanical properties of the resulting acrylic cement.
Nevertheless, the latter bone cements have also proved to be not without drawbacks. A first disadvantage is the fact that powdery tantalum, in contrast to tantalum in plaque form, is not considered biocompatible according to current regulations. The biocompatibility of tantalum is related to oxygen absorption, a phenomenon which is increased by the considerable specific surface area of the finely divided form necessary for efficient dispersion in the acrylic cement. Even if the cement is prepared immediately before use, it is almost impossible to prevent the oxygen from being absorbed by the metal and to keep its level at values below 300 ppm as required by the current regulations (ISO 13782), and the use of tantalum oxide is prohibited by the Pharmacopoeia.
A second drawback consists in the fact that the tantalum powder must be prepared by the surgeon at the moment of using it since, due to the sterility and biocompatibility requirements mentioned above, it is practically impossible to purchase tantalum powder in sterile form on the market.
A further drawback consists in the fact that it is difficult to obtain a diameter distribution of the particles forming the fine powder suitable for injection by means of a syringe.
A further drawback consists in the fact that the dispersion phase of the tantalum powder has the tendency to form inclusions of air in the bone cement.
A further drawback consists in the fact that it is extremely difficult to obtain a homogeneous dispersion of the powder in the polymer matrix.
International Patent Publication No. WO-A-9204924 discloses a radiopaque bone cement comprising a solid phase of polymethylmethacrylate powder and a liquid phase of polymethylmethacrylate monomer, wherein added to the solid phase are particles of radiopaque material coated with polymethylmethacrylate before mixing with the liquid phase. The radiopaque material is zirconium oxide or barium sulfate having diameter from 1 μm and 250 μm. However, the use of zirconium oxide or barium sulfate as radiopaque materials does not permit improvement of radiopacity combined with increased mechanical strength and fatigue resistance as specifically required for vertebroplasty. Moreover, the coating layer applied to the radiopaque materials of this prior art is aimed at avoiding the porosity and non-uniformity of the cement and therefore is not purported to prevent the formation of oxides.
International Patent Publication No. WO-A-9918894 discloses a bone cement specifically intended for vertebroplasty wherein the radiopaque material comprises particles of barium sulfate, tungsten or tantalum and therefore exhibits higher radiopacity as compared with the known bone cement compositions. However, the surface of the tungsten and/or tantalum particles used in Publication No. WO-A-9918894 is free of protection and has no coating to prevent oxygen absorption, and accordingly, some embodiments of this bone cement may be prohibited by the Pharmacopoeia. Morover, WO-A-9918894 gives no indication of the form of protection of the tungsten and/or tantalum particles used as radiopacifying agent.